Process for purifying cyclolipopeptide compounds or the salts thereof

Abstract

A process for purifying cyclic lipopeptide compounds or salts thereof comprising the steps of: (1) charging a crude compound of Formula I onto a macroporous adsorption resin; (2) washing the macroporous adsorption resin using water, an organic solvent or a mixed solution of an organic solvent and water as a washing liquid; and (3) eluting the compound of Formula I from the macroporous adsorption resin using water, an organic solvent or a mixed solution of an organic solvent and water as an eluent. The purification method has the advantages of using a small amount of organic solvents, using no silica gel, and causing little damage to the environment; the purity of the collected compound of formula I is also improved as compared with the methods previously disclosed.

The invention claimed is: 
     
       1. A method of purifying the compound of Formula I 
       
         
           
           
               
               
           
         
       
       or the salts thereof, said method comprising:
 loading the crude compound of Formula I onto a macroporous adsorption resin; 
 washing the macroporous adsorption resin using water, an organic solvent or a mixed solution of an organic solvent and water as the washing liquid, wherein said organic solvent comprises a C1-C4 alcohol or a C1-C4 ketone; and 
 eluting the compound of Formula I from the macroporous adsorption resin using water, an organic solvent or a mixed solution of an organic solvent and water as the eluent. 
 
     
     
       2. The purification process according to  claim 1 , wherein said loading comprises allowing a solution comprising the crude compound of Formula I to flow through a chromatographic column filled with the macroporous adsorption resin or mixing a solution comprising the crude compound of Formula I with the macroporous adsorption resin. 
     
     
       3. The purification process according to  claim 2 , wherein said loading comprises allowing a solution comprising the crude compound of Formula I to flow through a chromatographic column filled with the macroporous adsorption resin. 
     
     
       4. The purification process of  claim 1 , wherein the macroporous adsorption resin is selected from a non-polar aromatic adsorption resin polymerized from styrene and divinylbenzene, or a methacrylic adsorption resin of moderate polarity with methacrylate units in its structure. 
     
     
       5. The purification process according to  claim 4 , wherein the macroporous adsorption resin is selected from the group consisting of XAD-16, XAD-16HP, HP-20ss, SP-207, SP207ss, or the mixture thereof. 
     
     
       6. The purification process according to  claim 4 , wherein the adsorption resin comprises halogen and is bonded with styrene polymer matrix through chemistry bond. 
     
     
       7. The purification process according to  claim 6 , wherein the adsorption resin comprises bromine and is bonded with styrene polymer matrix through chemistry bond. 
     
     
       8. The purification process according to  claim 7 , wherein the adsorption resin is selected from: SP-207, SP-207ss, or a mixture thereof. 
     
     
       9. The purification process according to  claim 2 , wherein the solution comprising the crude compound of Formula I comprises ionizable salts, and the macroporous adsorption resin is selected from a non-polar aromatic adsorption resin polymerized from styrene and divinylbenzene. 
     
     
       10. The purification process according to  claim 9 , wherein the ionizable salt is selected from the group consisting of sulfates, nitrates, salts comprising halogen, phosphates, acetates, carbonates, citrates, silicates, persulfates, chromates, lactates, oxalates, and mixtures thereof. 
     
     
       11. The purification process according to  claim 1 , wherein the organic solvent is selected from the group consisting of methanol, ethanol, propanol, butanol, acetone, butanone, and mixtures thereof. 
     
     
       12. The purification process of  claim 1 , wherein in said washing, the volume percentage of the organic solvent is 0-3% based on the total volume of the washing liquid. 
     
     
       13. The purification process of  claim 1 , wherein in said eluting, the volume percentage of the organic solvent is 0-20% based on the total volume of the eluent. 
     
     
       14. The purification process of  claim 1 , wherein in said loading, the weight ratio of the crude compound of Formula I to the macroporous adsorption resin is 0.1-15 (g/L). 
     
     
       15. The purification process of  claim 3 , wherein said solution is allowed to flow at a flow rate ranging from 0.1 to 10 column volumes per hour. 
     
     
       16. The purification process of  claim 1 , wherein in said washing, the volume percentage of the organic solvent is 0-2%, based on the total volume of the washing liquid. 
     
     
       17. The purification process of  claim 1 , wherein in said eluting, the volume percentage of the organic solvent is 0-5%, based on the total volume of the eluent.